When one is diagnosed with diabetes, the long and short-term complications loom large over all of us. This month we discuss renal disease because diabetes has become the most common cause of end-stage renal disease (ESRD) in both the US and Europe.
We presume that all of you with diabetes are screened for microalbuminuria annually so that early intervention can be put into play. A new position paper on the subject by the ADA outlines the disease and, because we want you to have all of the information you need to make informed decisions about your health, we bring you the information you may need to live a long and healthy life. One may ask why diabetics make up such a large percentage of those with ESRD.
First, it may be related to the increasing numbers of people with type 2 diabetes.
Second, these people live longer.
Third, diabetics with ESRD are now accepted in programs for this disease from which they had been excluded in the past.
In the US, diabetic nephropathy makes up 40% of new cases of ESRD. About 20 to 30% of people with type 1 or type 2 diabetes develop nephropathy, but in type 2 diabetes, a much smaller fraction go on to ESRD.
However, because there are so many more people with type 2 diabetes, this population makes up over half of those diabetic patients currently starting on dialysis.
Racial/ethnic risk factors are higher for Native American, Hispanics (especially Mexican-Americans), and African-Americans for developing nephropathy. The good news is that studies show that diabetic nephropathy can be ameliorated to a significant degree by several interventions, but these have the greatest impact if started very early in the process of the development of this long term complication.
Our next question is what early symptoms of nephropathy are. This is defined as the appearance of low but normal levels of albumin in the urine, referred to as microalbuminuria. This is referred to as incipient nephropathy.
If there is no intervention, about 80% of people with type 1 diabetes who develop these symptoms will increase at the rate of 10-20% per year, to the stage of overt nephropathy or clinical albuminuria over a period of 10-15 years, with hypertension also developing in this time period.
Once overt nephropathy occurs without interventions, ESRD develops in 50% of type 1 diabetic persons with overt nephropathy within 10 years. A higher proportion of people with type 2 diabetes have microalbuminuria and overt nephropathy shortly after they are diagnosed with diabetes.
This is because diabetes can be present for years before it is diagnosed. Without interventions, 20-40% of type 2 diabetic patients with microalbuminuria progress to overt nephropathy, but by 20 years after onset only about 20% will progress to ESRD. Because of the high risk of this older population dying from associated coronary heart disease, many type 2 diabetes patients may not progress to ESRD.
It is hypothesized that as treatment for heart disease improves, more type 2 diabetic patients will go on to develop renal failure. One more fact that you need to know about albuminuria and that is that its presence is a marker of greatly increased cardiovascular morbidity and mortality in both type 1 and type 2 diabetes.
Therefore, if you or someone you love who has diabetes, develops this condition, make sure they have screening for possible vascular disease. Talk to your physician about instituting aggressive interventions to reduce all cardiovascular risk factors including lowering LDL cholesterol, anti-hypertensive therapy, stopping smoking, and beginning an exercise program.
Screening for microalbuminuria can be done three ways: The first is a measurement of the albumin-to-creatinine ratio in a random spot collection; the second is a 24-hour collection of creatinine, allowing the simultaneous measurement of creatinine clearance; and third, a timed, i.e. 4-hour or overnight collection.
Microalbuminuria is said to be present if urinary albumin excretion is greater than or equal to 30mg per 24 hours. Short term hyperglycemia, exercise, urinary tract infections, marked hypertension, heart failure and acute febrile illness can cause transient elevation in urinary albumin excretion.
Sometimes reagent strips are used, but these only indicate concentration and do not correct for creatinine urine concentration, so all positive tests should be confirmed by more specific methods.
There is also a marked day-to-day variability in albumin excretion, so at least two or three collections done in a three to six month period should be obtained before designating a person as having microalbuminuria.
Once ACE inhibitor or anti-otensin receptor blocker therapy for blood pressure control is started, the role of annual assessment is unclear, but many experts recommend continued surveillance to assess both the response to therapy and progression of the disease. In addition to evaluating urinary albumin excretion, assessment of glomerular function is important in people with diabetic kidney disease.
The DCCT and UKPDS have definitely shown that intensive diabetes therapy can significantly reduce the risk of developing microalbuminuria and overt nephropathy in people with diabetes.
In people with type 1 diabetes, hypertension is usually caused by underlying diabetic nephropathy and typically shows itself about the time people develop microalbuminuria.
In people with type 2 diabetes, hypertension is present at the time of diabetes diagnosis in about one-third of patients. The common coexistence of glucose intolerance, hypertension, elevated LDL cholesterol and triglycerides, and a reduction in HDL cholesterol, obesity, and susceptibility to cardiovascular disease suggests that they relate to common underlying mechanisms such as insulin resistance and the complex is often referred to as syndrome X or metabolic syndrome.
Do read our reports on this syndrome X and diabetes
In type 2 diabetes hypertension may be related to diabetic nephropathy or be due to coexisting “essential hypertension, or be due to a myriad of causes such as renal vascular disease.
In accordance with the “Standards of Medical Care for Patients with Diabetes Mellitus” the primary goal of therapy for non-pregnant diabetic patients 18 years of age or older is to decrease blood pressure and to maintain it at <130 mmHg systolic and <80 mmHg diastolic.
For patients with isolated systolic hypertension with a systolic pressure of greater than or equal to 180 mmHg, the initial goal of treatment is to gradually lower systolic blood pressure in stages. As goals are met and well tolerated, further lowering may be indicated.
If after 4-6 weeks, sufficient blood pressure reduction has not occurred, additional pharmacological therapy is indicated. In general, these medications may be added in a stepwise fashion and their individual use may be dependent on other factors such as fluid overload and vascular disease.
General recommendations for treatments:
A level evidence
- To reduce the risk and/or slow the progression of nephropathy, optimize glucose control.
- To reduce the risk and/or slow the progression of nephropathy, optimize blood pressure control.
- Expert consensus
- Perform an annual test for the presence of microalbuminuria in 1) type 1 diabetes patients who have had diabetes >5 years, and 2) all type 2 diabetic patients starting at diagnosis.
A level evidence
- In the treatment of albuminuria/nephropathy, both ACE inhibitors (antiotensin-converting enzyme)and ARBs (antiotensin receptor blocker) can be used: In hypertensive and non-hypertensive type 1 diabetic patients with any degree of albuminuria, ACE inhibitors have been shown to delay the progression of nephropathy.
- In hypertensive type 2 diabetic patients with microalbuminuria, ACE inhibitors and ARBs have been shown to delay the progression to microalbuminuria.
- In patients with type 2 diabetes, hypertension, microalbuminuria, and renal insufficiency (serum creatinine >1.5 mg/dl), ARBs have been shown to delay the progression of nephropathy.
With the onset of overt nephropathy, initiate protein restriction to less than or equal 0.8g per kg of body weight per day (about 10% of daily calories), the current RDA for protein. Further restriction may be useful in slowing the decline of GFR (glomerular filtration rate) in selected patients.
If ACE inhibitors or ARBs are used, monitor serum potassium levels for the development of hyperkalemia.
Consider referral to a physician experienced in the care of diabetic renal disease when either the GRF has fallen to levels of concern or difficulties have occurred in the management of hypertension or hyperkalemia. Consider the use of non-DCCBs (dihydropyridine calcium channel blocker) or beta-blockers in patients unable to tolerate ACE inhibitors or ARBs.
To summarize, annual screening for microalbuminuria will identify people with diabetic nephropathy at a time early in process. Improving glycemic control, aggressive anti-hypertensive treatment, and the use of ACE inhibitors or ARBs will slow the progression of nephropathy. In addition, protein restriction and other treatment modalities such as phosphate lowering may have benefits in some patients.
The most important thing is that you know your risk factors and make sure that your medical team is attentive to your needs. Now you have some of the buzzwords, and know the medications and other interventions. You know the tests and you know what questions to ask, so take care of yourself and live well.